Innovations in Bioinformatics: Emerging tools for drug discovery and development

Innovations in Bioinformatics: Emerging tools for drug discovery and development

R&D laboratories are co-ordinating the analysis of increasing volumes of disparate biological data, largely comprised of gene and protein sequences. Bioinformatics-enabled data management has enabled companies to improve productivity within their R&D programmes by identifying new drug targets, diagnostic biomarkers and biomarkers of drug efficacy and toxicity. From a systems biology approach, bioinformatics combine data into interactive models to highlight disease pathways and aid the discovery of on off-target effects of compounds. Knowledge management solutions are crucial in both instances, enabling project teams to make informed decisions about potential new drugs.  Innovations in Bioinformatics is a new report published by Business Insights that provides a detailed analysis of bioinformatic developments and applications. This report examines the bioinformatic tools used to manage high-throughput data from omic technologies, systems biology modelling and biomarker discovery. Knowledge management solutions are reviewed and the provisions of major bioinformatics contributors are highlighted. This report also provides forecasts for bioinformatic tools and services to 2011. Use this new report to identify the latest developments in bioinformatics, assess the tools and platforms that can improve drug developments and benchmark effective implementation strategies.

Table of Contents
Innovations in Bioinformatics: Emerging tools for drug
discovery and development
Executive Summary 12
Bioinformatics in the omics era 12
Genomics and related  omics 13
Proteomics 14
Metabolomics and systems biology 15
Knowledge management solutions 17
Profiles of selected companies 18
Trends and opportunities 19
Chapter 1 Bioinformatics in the omics era 22
What is bioinformatics? 23
End-users of bioinformatics tools and services 23
Life sciences in the omics era 24
Overview of omics 26
Genomics 26
Pharmacogenomics 27
Transcriptomics 27
Proteomics 28
Metabolomics 28
Other omics 28
Background on drug discovery and development 29
Types of drugs under development 29
Small molecules 29
Protein-based biotherapies 30
Nucleic acid-based biotherapies 31
The drug discovery and development process 31
Stages (US) 31
Role of biomarkers 33
Bioinformatics in drug discovery and development 34
From biological data to drug knowledge 35
Chapter 2 Genomics and related omics 38
Summary 38
Background 39
Categories of genomic analysis 40
Sequencing 40
Next-generation sequencing 42
Genotyping and gene expression 44
DNA microarrays 45
Value of genomic analysis to the drug industry 46
Bioinformatics solutions 50
Analysis of sequencing data 50
Sequence databases 52
Sequence search tools 56
Multiple sequence alignment tools 61
Focus on RNAs 63
Genome finishing and annotating 71
Microarray platforms 74
Affymetrix 75
Illumina 76
Agilent Technologies 78
Applied Biosystems 79
Genome-wide association studies 79
Other advances 81
Chapter 3 Proteomics 86
Summary 86
Background 87
Categories of proteomic analysis 88
Protein separation 89
Protein identification 90
Mass spectrometry 90
Protein microarrays 91
Structure determination 91
Value of proteomic analysis to the drug industry 92
Bioinformatics solutions 94
Analysis of sequencing data 95
Sequence databases 95
Sequence search tools 110
Multiple sequence alignment tools 111
In silico drug discovery 111
Data analysis and integration 113
Agilent Technologies 114
Applied Biosystems 114
BioWisdom 115
Bruker Daltonics 116
Geneva Bioinformatics 116
GeneLogics 118
Health Discovery Corporation 119
Nonlinear Dynamics 119
Sage-N Research 120
Thermo Scientific 121
Vermillion 121
Chapter 4 Metabolomics and Systems
Biology 124
Summary 124
Background 125
Metabolomics 126
Introduction 126
Value to the drug industry 127
Commercial bioinformatics solutions 128
Systems biology 129
Introduction 129
Value to the drug industry 131
Initiatives at Big Pharma 132
Approaches 132
In silico mathematical models 134
The Systems Biology Markup Language 135
Publicly available modeling software 137
Commercial pathway analysis tools 144
Ariadne Genomics 144
GeneGo 145
Ingenuity Systems 145
Commercial modeling technologies 146
BG Medicine 147
Cellnomica 148
Compugen 148
CuraGen 149
Entelos 150
Genstruct 150
Genomatix 152
Genomatica 152
Gene Network Sciences 153
Health Discovery Corporation 154
Merrimack Pharmaceuticals 155
Physiomics 155
Chapter 5 Knowledge Management
Solutions 158
Summary 158
Introduction 159
Providers of high-performance computing 160
Providers of storage systems 164
Web-based solutions 165
Ontologies 166
Knowledge sharing 167
The Semantic Web 169
Software to support R&D labs 170
Abrevity 172
Accelrys 172
Agilent Technologies 172
BioWisdom 173
CambridgeSoft 173
Elsevier MDL 174
Geospiza 174
GeneLogics 174
IO Informatics 174
KOOPrime 175
LabVantage 175
MathWorks 175
NextBio 176
Oracle 176
SAS 176
Symyx 177
Teranode 177
Thermo Fisher Scientific 177
Text searching and mining 178
QUOSA 178
Linguamatics 178
Inforsense 179
Insightful 179
Nervana 180
Velocity 180
Clinical trials solutions 180
Adobe Systems 182
Infosys 182
Oracle 182
Pharsight 183
Chapter 6 Profiles of selected companies 186
Summary 186
Accelrys Inc 187
Company overview 187
Bioinformatics tools and services 188
Bioinformatics-related collaborations 189
Affymetrix Inc 189
Company overview 189
Bioinformatics tools and services 191
Agilent Technologies Inc 191
Company overview 192
Bioinformatics tools and services 193
Avalon Pharmaceuticals Inc 194
Company overview 194
Bioinformatics-related collaborations 195
BG Medicine Inc 196
Company overview 196
Bioinformatics tools and services 197
BioWisdom Ltd 198
Company overview 198
Bioinformatics tools and services 198
Caliper Life Sciences Inc 200
Company overview 200
Bioinformatics tools and services 201
Compugen Ltd 202
Company overview 202
Bioinformatics tools and services 203
Bioinformatics-related collaborations 204
CuraGen Corporation 205
Company overview 205
Bioinformatics tools and services 206
Entelos Inc 207
Company overview 207
Bioinformatics tools and services 208
Genstruct Inc 209
Company overview 209
Bioinformatics tools and services 210
Bioinformatics-related collaborations 211
Gene Network Sciences Inc 212
Company overview 212
Bioinformatics tools and services 212
Bioinformatics-related collaborations 213
GeneGo Inc 213
Company overview 214
Bioinformatics tools and services 214
Bioinformatics-related collaborations 215
Health Discovery Corporation 216
Company overview 216
Bioinformatics tools and services 217
Illumina Inc 218
Company overview 219
Bioinformatics tools and services 220
Bioinformatics-related collaborations 220
Ingenuity Systems Inc 221
Company overview 221
Bioinformatics tools and services 222
Bioinformatics-related collaborations 223
Insightful Corp 224
Company overview 224
Bioinformatics tools and services 225
Bioinformatics-related collaborations 226
NextBio 226
Company overview 226
Bioinformatics tools and services 227
Bioinformatics-related collaborations 228
SAS Institute Inc 228
Company overview 228
Bioinformatics tools and services 229
Bioinformatics-related collaborations 229
Vermillion Inc 230
Company overview 230
Bioinformatics tools and services 231
Chapter 7 Trends and opportunities 234
Summary 234
End-user needs and sentiment 235
Emerging trends in market evolution 237
Bioinformatics-enabled biomarker discovery 239
The promise of Semantic Web technology 240
Facilitating implementation of IT systems 242
Market snapshot and forecasts 243
Genomics and related omics 243
Proteomics 244
Systems biology 245
Life science enterprise knowledge management 245
Market estimates 246
Chapter 8 Appendix 249
Research methodology 249
Index 250
List of Figures
Figure 2.1: An entry from Entrez GENE, the US NCBI's web-based interface to GENBANK 55
Figure 2.2: Genomic context of the myostatin gene (GDF8) using the NCBI Map Viewer 56
Figure 2.3: Search page of microInspector 67
Figure 2.4: Search page of the miRNA database (miRBase) 68
Figure 2.5: miRBase Targets database, a new resource for predicting miRNA targets in animals69
Figure 2.6: Predicted Human Genomic Targets for the hsa-let-7g* miRNA 69
Figure 2.7: Dharmacon siRNA Designer Search Page 70
Figure 3.8: Advanced Search page of the Protein Data Bank (PDB), the central repository for 3D protein structure information 99
Figure 3.9: PDB Entry for the complex of the acetylcholine receptor with carbamylcholine (1UV6) 99
Figure 3.10: Results of a search in the UniProt KnowledgeBase (Swiss-PROT and TrEMBL) for MAP kinase phosphatases 101
Figure 3.11: Partial UniProt record for Dual Specificity Protein Phosphatase 4 (DUSP4) / MAP
Kinase Phosphatase 2 103
Figure 3.12: UniProt Feature Aligner for Dual Specificity Protein Phosphatase 4 (DUSP4) 104
Figure 3.13: UniProt sequences at least 90% similar to Dual Specificity Protein Phosphatase 4 (DUSP4) 105
Figure 3.14: Front page of the Protein Kinase Resource, University of California at San Diego 106
Figure 3.15: UniProt sequences at least 90% similar to Dual Specificity Protein Phosphatase 4 (DUSP4) 107
Figure 4.16: Genomatica's SimPheny"! Systems Biology Model Development Process 153
List of Tables
Table 2.1: Bioinformatic Analyses of DNA/RNA Sequences 50
Table 2.2: Contribution of Bioinformatics to Genomics-Based Drug Discovery 50
Table 2.3: Databases and On-line Tools for Analyzing DNA Sequences and Signals 53
Table 2.4: Leading Sequence Comparison Servers 57
Table 2.5: BLAST Applications and Flavors 58
Table 2.6: Online Pairwise Alignment Programs 60
Table 2.7: Multiple Sequence Alignment Tools 62
Table 2.8: RNA Secondary Structure Prediction 64
Table 2.9: miRNA and siRNA Resources 65
Table 2.10: Selected genome-sequencing packages 72
Table 2.11: Phylogeny and Orthology 73
Table 2.12: Summary of patent-related genes in the major organisms 74
Table 3.13: Role of Bioinformatics in Protein Diagnostics and Therapeutics 94
Table 3.14: Selected Protein Databases 96
Table 3.15: On-line tools to test for protein transmembrane segments 108
Table 3.16: Principal Protein Domain Recognition Resources 109
Table 3.17: Protein Structure Prediction 110
Table 4.18: Software for Systems Biology 138
Table 7.19: World Bioinformatics Market, 2006-2011 248